It is known that epithelial layer damage causes transepithelial difference of potentials [1, 2], an increase in endogenous electric fields of the wound and, as a result, accelerated wound healing. An increase in the electric field strength induced by a cathode applied to the wound increases the rate of epithelium motion to the wound [3].
Additionally, the association between the cell membrane potential and cancer was observed in many studies performed for normal and transformed cell lines.
Cone [4] suggested based on these data that the transmembrane potential can control the mitotic cycle. The main idea is that a decrease in the membrane potential initiates the cell cycle. He explains oncogenesis assuming that the cell after mitosis loses the capability to restore its normal electronegative cell membrane potential and, consequently, has to repeat the cell cycle. Later this assumption was confirmed by different authors. For example, Marino et al. [5] showed that the average cell membrane potential of breast with infiltrating ductal carcinoma was highly depolarized compared to the values measured in tissues with breast benign disease. Depolarization was also observed in transformed epithelial breast cells compared to normal breast cells.
Binggeli et al. [6] revealed differences in the electrical properties of normal and cancer cells. Comparison of the membrane potential of normal and transformed cells showed that cancer cells (sarcomas) have lower negative potential (e.g., the normal cell potential is 42.5±5.4 mV, and cancer cell potential is 14.3±5.4 mV).
Sundelacruz et al. [7] showed that by regulating the cell membrane potential, as well as that of cancer cells, it is possible to control their proliferation and differentiation.
It is known that nano- and microstructured hydroxides and oxyhydroxides are used in various materials and technological processes, in biology and medicine.
There is a method of producing an improved fibrous filtering material [RU 2011116705 A, publ. 10 Nov. 2012] wherein an aluminum and silicon oxyhydroxide layer with positive surface charge is formed on the surface of a fibrous material, for which an Al2O3—SiO2 solution is prepared and deposited on a fibrous ceramic material.
Disadvantages of this method are that the positive surface charge is generated based on the known properties of structured silicon whose coatings are formed in treatment of the fibrous ceramic material.
There is a one-nanometer positive fiber adsorbent, described in [RU 2304463 C2, publ. 20 Aug. 2007], which consists of non-spherical aluminum oxyhydroxide particles shaped as fibers of diameter less than 50 nm and having the length to thickness ratio of more than five to one. The adsorbent is produced in a reaction of interaction between initial aluminum component and water solution at a temperature of up to 100° C. and applied directly to the fiber surface. It has a capability to adsorb at least one electronegative particle from the liquid.
There is a method of producing nanofibers of oxide-hydroxide phases with boehmite structure [RU 2328447 C1, publ. 10 Jul. 2008] which can be applied to produce adsorbents for fine purification of drinking water, industrial and waste water. The nanofibers of aluminum oxide-hydroxide phases are produced by hydrolysis of powder synthesized by electrical explosion of aluminum wire of diameter 0.3<d≤0.4 mm in nitrogen atmosphere under pressure P<3 atm and energy 19.8 J/mm3<E≤66 J/mm3 applied to the wire. Subsequent powder hydrolysis is carried out at a temperature of more than 70° C. The produced nanofibers of aluminum oxide-hydroxide phases have the length 0.1-0.2 μm, diameter 0.001-0.013 μm and specific surface area up to 500 m2/g.
Patent [U.S. Pat. No. 8,033,400 B2, publ. 11 Oct. 2011] discloses a filtering material produced on the basis of nonwoven organic synthetic polymeric fabric and positively charged agglomerates of aluminum hydroxide nanofibers. Patent [RU 2397781 C1, publ. 27 Aug. 2010] discloses a nonwoven material for medical purposes which has wound healing, antibacterial and antiviral activity, and wound dressings on its basis made of a fibrous material with highly porous alumina hydrate particles fixed on its fibers.
A disadvantage of the known nanosized fibrous adsorbents described in [RU2304463 C2 and RU 2328447 C1, RU 2397781 C1, U.S. Pat. No. 8,033,400 B2] are a relatively low sorption capacity due to the shape and arrangement of fibers or nanofibers. This is confirmed by the data provided by Tepper and Kaledin in the paper “Virus and Protein Separation Using Nano Alumina Fiber Media” [http://www.argonide.com/publications/laboratory.pdf]. The paper contains micrographs of nanofibers that form close-packed structures. As a result, the pore space of the sorption nanofibrous material is less accessible to the sorbate (bacteria, colloidal particles, etc.) than the pore space of agglomerates of low-dimensional folded structures. The micrographs demonstrate that colloidal particles are primarily adsorbed to nanofiber ends, rather than between nanofibers. Consequently, nanofibers with large specific surface area have low sorption capacity.
Larichev et al. [8] studied the hydrolysis of commercial aluminum powder of grade ASD-4 with an average grain size of about 4 μm produced in Russia. The authors investigated aluminum oxidation in distilled water and in the Ca(OH)2 saturated aqueous solution (buffer activator) with and without ultrasonic field application. The degree of ASD-4 oxidation in distilled water for a reasonable time (a few days) without an ultrasonic field does not exceed 30%. A cellular structure of oxidation products is formed on the surface of the initial aluminum particles. A combination of ultrasonic and buffer activation considerably changes the process, the oxidation degree increases to 100%. In this case, rod-shaped nanostructures are formed. The BET surface area of such products is only 40 m2/g.
The aforementioned rod-shaped nanostructures have small specific surface area and hence their sorption properties might be low. No data are provided on whether these nanofibers can generate an electric field in aqueous media.
There is a process for the preparation of an adsorbent containing iron oxyhydroxide FeO(OH), adsorbent material and use thereof, described in [WO2006032727 (A1), publ. 2006 Mar. 30]. The invention relates to a process for producing an adsorbent material that contains iron oxyhydroxide, wherein an iron oxyhydroxide mass with a moisture content of 5-15 wt % is produced, the mass is granulated by compaction, followed by comminution and sieving of the compacted product to give product granules of grain size ranging from 0.5 to 4 mm.
The disclosed adsorbent represents granules of size ranging from 0.5 to 4.0 mm Granules of this size would not generate a high-strength electric field which is necessary for effective adsorption of charged particles and for the effect on cell membranes.
There is a method of producing biopreparation ferrigel [RU 2466713, publ. 20 Nov. 2012] on the basis of nanosized ferric oxyhydroxide. The biopreparation is produced by mixing ferric oxyhydroxide recovered at underwater deferrization stations with water soluble polymer and glycerol.
The patent description provides no information on the shape of the ferric oxyhydroxide particles and on the properties responsible for their biological activity, such as accelerated wound healing. Moreover, the ferric oxyhydroxide particles mixed with water soluble polymers and glycerol would be coated with these substances and hence a larger part of their surface would be inaccessible for biological objects.
There are polymer materials for wound healing and cancer cell inhibition.
Patent [RU 2471349, publ. 10 Jan. 2013] discloses a polymer material for elimination of live target cells. The material contains at least one insoluble hydrophobic anionic, cationic or amphoteric charged polymer. The polymer in contact with water-containing environment:                a) is a carrier of strongly acidic or strongly basic functional groups;        b) has a pH value lower than 4.5 or higher than 8.0; and        c) possesses proton conductivity and/or electrical potential sufficient for the disruption of pH homeostasis and/or electrical balance inside the closed cell volume.        
The charged polymer preserves the pH value of the medium, changing the pH value only within the cell. The shift of the aqueous medium pH to the acidic (pH less than 4.5) or alkaline range (pH higher than 8.0) induces cell death in prokaryotes and eukaryotes. The said material can be regenerated by the regeneration of charged polymer, buffer capacity and proton conductivity of the material.
The suggested cell death mechanism associated with pH and/or electric balance change in the cell volume is in doubt. This mechanism has no evidential basis because modern science and technology do not permit the measurement of pH and/or electric balance within the cell. The data and examples provided in the patent indicate that cell death induces a local pH change in the aqueous medium surrounding the cell; pH of the entire medium can remain unchanged due to low concentration of the active material. According to the disclosure, the object of the invention is to produce materials (insoluble proton reservoirs or sources) containing easily dissociated cationic and/or anionic groups spatially arranged so that to effectively minimize pH change in a medium” i.e. a minimum pH change of the medium was observed. As is known from chemistry, when a substance disassociates into ions, they inevitably appear in the medium.
Cells are thus affected due to the formation of conditions on the cell surface or in the vicinity of cells (high or low pH values) under which both cancer and normal cells cannot live. The use of such materials for the treatment of oncological patients or for the application as an antimicrobial agent is therefore greatly restricted.
There is a polymer electret healing film (applicator) Polymedel [9]. The electrets used in surgery activate reparative processes in chronic nonhealing wounds, pressure ulcers, neurotrophic ulcers and thermal injuries. The rate of necrotic tissue reduction in the wound decreases significantly, substantial wound granulation is accelerated, epithelization of wound edges begins earlier, transition of the process from the second to the third stage (damage through entire skin) and from the third to the fourth stage (destruction of skin and underlying tissue) is inhibited or even stops. Recent studies showed that an electret applied to various painful regions reduces pain (arthritis, osteochondrosis, radiculitis, bruises, renal colics and so on). An applied electric field causes microvibration and microconvection within a biological tissue which are induced by electrohydrodynamic forces. This changes the rate of metabolic processes, cell permeability, the rate of reagent delivery to membrane surfaces and macromolecules.
Disadvantages of electret films are that cells are affected indirectly, via microvibration and microconvection arising within biological tissue under the action of electrohydrodynamic forces. There is no direct influence on the cell membrane potential. Consequently, the electret film efficiency is low. The application of polymer electret film on wounds with heavy or purulent drainage would reduce air flow to the wound, which is inadmissible and can make a disease worse. There is also no documented evidence on oncological diseases cured with the use of electret materials.
There are physical methods of cancer cell treatment using an electric field.
There is a method for treating pathological proliferation of body cells [RU 2270663 C2, publ. 27 Feb. 2006] wherein biologically active points are chosen and treated. A biologically active point corresponding to an organ with pathological cell proliferation is chosen and the potential of the chosen point is measured with respect to a reference point. Then, an external source of direct electric field is attached to the chosen points. The poles of this source should be opposite in sign to the poles of the points, and its absolute value should be equal to the difference of the absolute values of the measured potential and the potential corresponding to the healthy organ in the chosen point. The electric field is applied until the cancer cell membrane potential reaches the membrane potential of the healthy organ. As a result, biochemical processes in cells are normalized, due to which the pathological activity of cancer cells is significantly reduced and, in the limiting case, cells recover their normal state.
There is a method of stopping carcinoma cell division [RU2253903, publ. 10 Jun. 2005] based on exposing a cell or a group of cells to an external energy source, wherein at least two electrodes are applied before treating the cells. One of the electrodes is attached to the cytoplasmatic side of the cell membrane and the other is attached to the outer cell membrane surface to measure the membrane potential. Then, an external voltage source with reverse polarity whose potential difference is not less than the cell membrane potential is connected to the attached electrodes.
The methods of tumor cell growth inhibition disclosed in Patents RU2270663 and RU2253903 are based on the action of the electrical potential on cell membranes from electrodes attached to the tumor. These methods are complicated and traumatic. Moreover, only cells directly contacting with the electrode surface are killed. Tumor cells not contacting with the potential electrodes survive.
There is also an electropositive compound against cancer [10] that works on the basis of positively charged molecules F16. An F16 molecule is attracted by negatively charged cancer cell mitochondria and adheres to them. Mitochondria of various cancer cells have higher negative charge. As a result, F16 are accumulated in cancer cell mitochondria, leading to tumor cell death. Electron microscopic studies showed that F16 induces mitochondria swelling, due to which outer cell membranes are damaged and the tumor cell dies.
A disadvantage of this compound is that molecules F16 can accumulate not only in cancer cell mitochondria but also in normal cells that are also negatively charged, which can lead to their death.
As one can see from the above-discussed analogs, metal oxyhydroxides, polymer materials and molecules capable of selectively affect living cells due to electric charge application to biological structures.
These properties are used for microorganism sorption, wound healing, pain syndrome treatment and tumor cell growth inhibition. Today, however, there is a particular demand for materials with higher sorption capacity and higher biological activity which can be achieved by modifying the electrical properties of materials.